Hematologic cancers are cancers “of the blood system.” These cancers usually affect the white blood cells (disease and infection-fighting cells) rather than the red blood cells (oxygen-carrying cells). Some of these cancers are in the marrow where all blood cells are made. Some are in the lymph nodes and other lymph tissues that the white blood cells flow through. Common cancers of the white blood cells are the leukemias, Hodgkin's lymphoma, other lymphomas and multiple myeloma.
Multiple myeloma (MM) is a B-cell malignancy that accounts for approximately 1% of all types of human cancer, being more common than myelocytic leukemia or Hodgkin's disease.
Multiple myeloma can cause anemia, severe bone pain, and in some cases pathological fracture, increased risk of infection, hypercalcaemia and renal failure. While chemotherapy is the preferred initial treatment for symptomatic MM, the disease is highly resistant to chemotherapeutic agents and most patients who initially respond to such treatment eventually relapse.
A new approach in controlling cancer progression is through the use of oncolytic viruses. Oncolytic viruses are viruses that are able to selectively destroy or “lyse” malignant cells, while leaving normal host cells intact. A number of human solid cancers are susceptible to the oncolytic activity of numerous viruses, which each possess unique biologies to mediate selective oncolysis. Reovirus (Alain T, et al. Blood. 2002; 100:4146-4153; Thirukkumaran C M, et al. Blood. 2003; 102:377-387), measles virus (Grote D, et al. Blood. 2001; 97:3746-3754), and Newcastle disease virus (Schirrmacher V, et al. Int J Oncol. 2001; 18:945-952), are among three known oncolytic viruses that may be effective against some malignancies.
Recently it was demonstrated that a common cold virus, Coxsackievirus A21 (CVA21) was effective against human melanoma xenografts in an immune-deficient mouse model (Shafren D R, et al. Clin Cancer Res. 2004; 10:53-60). CVA21 is an enterovirus known to selectively utilize the cell surface molecules intercellular-adhesion molecule 1 (ICAM-1) and decay-accelerating factor (DAF) to mediate infection of cells. Although CVA21 can bind to DAF, ICAM-1 is the key receptor for CVA21 infection of cells—as without ICAM-1 expression on the cell surface, CVA21 is unable to gain cell entry and attain infection of the host cell under normal conditions.
The present applicant previously developed new methods for treating solid tumor malignancies using oncolytic viruses that recognise ICAM-1 (PCT/AU00/01461 (WO 01/37866) entitled “A Method of Treating a Malignancy in a Subject and a Pharmaceutical Composition For Use in Same”). Excellent therapeutic results were obtained by using various Coxsackievirus A strains on a number of solid tumor cell types. New methods for the treatment of abnormal cells, such as cancer cells, in mammals using viruses such as Echoviruses which recognise integrin α2β1 for infectivity of the cells were also developed by the present applicant (PCT/AU2003/001688 (WO2004/054613) entitled “A method of treating a malignancy in a subject via direct Picornaviral-mediated oncolysis”). In order to expand the possible cancer treatment and provide even more efficacious treatments, the present inventors have surprisingly found that Picornavirus isolates may also be suitable as oncolytic agents in hematologic cancers.